Role and environment of the conserved Lys27 of snake curaremimetic toxins as probed by chemical modifications, site‐directed mutagenesis and photolabelling experiments

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Abstract
The positive charge of Lys27 was supressed by chemical means in two short‐chain curaremimetic toxins, namely erabutoxin a (Ea) from Laticauda semifasciata and toxin α from Naja nigricollis. This modification leads to a decrease in the binding affinity of the toxins for the nicotinic acetylcholine receptor, which range 6–15‐fold, as judged from both the data reported here and those previously described in the literature. A negatively charged glutamate residue has been introduced at position 27 of erabutoxin a by site‐directed mutagenesis. This change provokes a 120‐fold decrease in the affinity, which reflects a major alteration of toxin‐receptor cognate events.Using toxin‐α derivative harbouring a photoactive group at Lys27, we probed the toxin local environment in a receptor‐bound state by photocoupling experiments. The δ chain was the predominant coupling target, in contrast to previous observations indicating that a photoactive probe on Lys47 predominantly labelled the α chain. The toxin derivative weakly labelled the α and γ chains but not the β chain. The toxin may therefore interact with subunits other than the α chain, at least in the vicinity of Lys27.

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